Needle Structures and Methods for Fabricating Needle Structures

ABSTRACT

A needle comprising: a base portion; a stem portion extending from the base portion; a tip portion formed on the stem portion; wherein a length of the stem portion is chosen such that the needle can be used for intradermal or subcutaneous drug delivery, and the base portion, the stem portion and the tip portion are integrally formed.

FIELD OF INVENTION

The present invention relates broadly to needle structures and methodsfor fabricating needle structures.

BACKGROUND

Needle structures such as needles and microneedles are being utilised invarious technology fields, for example, in the administration of drugsto a body. Drugs can be administered to the body by, for example,injection. A typical injection operation involves a syringe with aneedle which is first used to breach the skin and then to be inserted toreach a desired depth in the body before the drug is injected into thebody. There are various modes of delivery of drugs into the body, forexample, transdermal delivery, intradermal delivery, subcutaneousdelivery, intramuscular delivery, intravenous delivery, etc., whichdeliver drugs to different parts of the body at different depths.Generally, needle structures should be sharp and robust enough to piercethe skin for the administration of drugs into the body.

The use of conventional microneedles is generally limited to thetransdermal mode of delivery of drugs into the body, where themicroneedles are inserted through the stratum corneum (SC) and theepidermis layer to deliver drugs shallowly into the skin.

Conventional needles are used for delivery modes such as intradermaldelivery, subcutaneous delivery, intramuscular deliver and intravenousdelivery where the needles are inserted into greater depths of the bodybeyond the stratum corneum and epidermis layer of the skin. For example,in the intradermal delivery mode, the needle is inserted within thedermis layer of the skin (beyond the epidermis layer). In subcutaneousdelivery, the needle is inserted beyond the thickness of the skin.Intramuscular delivery and intravenous delivery involves inserting theneedle into the muscles and veins, respectively, and can generally beclassified as a form of subcutaneous delivery. However, thesetraditional needles are made of metal and are complicated and costly tomanufacture. The traditional metal needles are usually fabricatedseparately and an assembly step is required to assemble the needle withanother part, e.g. a luer connector in order for the needle to beattached to a syringe and the needle may require post fabricationmachining. Further, customisation of metal needles with complex shapesor geometries can be very difficult to achieve, if not impossible.Further more, fabrication of metal needles is not cost effective due topost fabrication processes such as assembling to the luer connector andcustomisation of needle geometry.

Therefore, there is a need for alternative needle structures and methodsof fabricating the needle structures for intradermal delivery andsubcutaneous delivery of drugs into the body.

SUMMARY

According to a first aspect of the present invention, there is provideda needle comprising: a base portion; a stem portion extending from thebase portion; a tip portion formed on the stem portion; wherein a lengthof the stem portion is chosen such that the needle can be used forintradermal or subcutaneous drug delivery, and the base portion, thestem portion and the tip portion are integrally formed.

The base portion, the stem portion and the tip portion may be integrallyformed from the same material.

At least one of the base portion, the stem portion or the tip portionmay be integrally formed from a different material.

The needle may further comprise: at least one side port; and

a lumen extending within the needle, the lumen extending from the baseportion to the stem portion and the tip portion, wherein the side portextends into the lumen such that the side port and the lumen are influid communication with each other.

The lumen may comprise a plurality of sections, each section having adifferent diameter or width.

The diameter or widths of the plurality of sections may be in descendingorder starting from a base section of the lumen.

The lumen may be tapered.

The needle may comprise two or more side ports disposed on the tipportion of the needle.

The needle may further comprise an extended tip portion formed on thetip portion, the extended tip portion forming an apex of the needle,wherein the extended tip portion comprises a substantially elongateprotrusion extending from the tip portion.

A geometry of the extended tip portion may be substantially the same ordifferent from a geometry of the tip portion.

The base portion may comprise a connection adapter for coupling to adispensing apparatus.

The base portion may comprise a luer lock structure for interconnectingthe needle to a syringe.

The base portion may comprise a barrel portion, the barrel portion beingadapted for coupling to a plunger.

The needle may be made from at least one of a group of polymersconsisting of polycarbonate (PC), polystyrene (PS), polyetherimide(PEI), polyetherehterketone (PEEK).

The needle may be fabricated using injection moulding or cast mouldingor derivatives of cast moulding or injection moulding.

According to a second aspect of the present invention, there is provideda method of fabricating a needle, the method comprising: forming a baseportion; forming a stem portion extending from the base portion; forminga tip portion formed on the stem portion; wherein a length of the stemportion is chosen such that the needle can be used for intradermal orsubcutaneous drug delivery, and the base portion, the stem portion andthe tip portion are integrally formed.

The base portion, the stem portion and the tip portion may be integrallyformed from the same material.

At least one of the base portion, the stem portion or the tip portionmay be integrally formed from a different material.

The method may further comprise: forming at least one side port; and

forming a lumen extending within the needle, the lumen extending fromthe base portion to the stem portion and the tip portion, wherein theside port extends into the lumen such that the side port and the lumenare in fluid communication with each other.

The lumen may comprise a plurality of sections, each section having adifferent diameter or width.

The diameter or widths of the plurality of sections may be in descendingorder starting from a base section of the lumen.

The lumen may be tapered.

The method may further comprise: two or more side ports disposed on thetip portion of the needle.

The method may further comprise: forming an extended tip portion on thetip portion, wherein the extended tip portion forms an apex of theneedle and the extended tip portion comprises a substantially elongateprotrusion extending from the tip portion.

The base portion may comprise a connection adapter for coupling to adispensing apparatus.

The base portion may comprise a luer lock structure for interconnectingthe needle to a syringe.

The base portion may comprise a barrel portion, the barrel portion beingadapted for coupling to a plunger.

The method may further comprise: forming a master mould comprising apositive shape of the needle; using the master mould to form aproduction mould comprising a cavity comprising a periphery of anegative shape of the needle; and using the production mould to form theneedle.

The method may comprise: forming the master mould comprising a positiveshape of the needle; using the master mould to form an intermediatemould comprising a cavity comprising a periphery of a negative shape ofthe needle; and using the intermediate mould to form the productionmould.

The method may comprise: forming a pair of production mould halves, eachproduction mould halve comprising a cavity comprising a periphery of anegative shape of the needle; using the pair of production mould halvesto form the needle.

The method may comprise: forming a pair of intermediate mould halves,each intermediate mould halve comprising a cavity comprising a peripheryof a negative shape of the needle; using the pair of intermediate mouldhalves to form a pair of production mould halves.

The pair of production mould halves may be identical to each other, eachproduction mould halve comprising a plurality of cavities, each cavitycomprising a periphery of a negative shape of the needle.

The periphery of the negative shape of the needle may be substantiallyparallel to an interface of the two production mould halves.

The intermediate mould halves may be made from polymer.

The method may further comprise: filling the cavity of the productionmould halves with a polymer to form the needle.

The positive shape of the needle on the master mould may be created byprecision wire-cutting.

The production mould halves may be made of metal.

The method may further comprise: providing an insert member;

providing the pair of production mould halves, each of the productionmould halves further comprising at least one slot portion for receivingand aligning the insert member such that a leading edge of the insertintersects the periphery of the negative shape of the needle; aligningthe pair of production mould halves; inserting the insert member intothe production mould halves; and filling the production mould halveswith a fill material, wherein the insert creates the lumen in the needleand the intersection of the leading edge of the insert with theperiphery of the negative shape of the needle creates the side portextending into the lumen such that the lumen and the side port are influid communication with each other.

The periphery of the negative shape of the needle may comprise a channelextending from an apex of the negative shape of the needle for formingthe extended tip portion of the needle.

The method may further comprise filling the channel at least partiallyto form the extended tip portion.

The insert member may comprise a pin having a plurality of sections,each section having a different diameter or width.

The pin may be tapered.

According to a third aspect of the present invention, there is provideda use of a needle for injecting liquid into a body.

According to a fourth aspect of the present invention, there is provideda use of a needle for extracting body fluid from a body.

Extracting body fluid from the body may include whole blood sampling.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the invention will be better understood and readilyapparent to one of ordinary skill in the art from the following writtendescription, by way of example only, and in conjunction with thedrawings, in which:

FIG. 1( a) is a schematic isometric view of a needle;

FIG. 1( b) is a schematic drawing of a the needle of FIG. 1( a);

FIG. 2 is a schematic drawing of a needle breaching the skin forintradermal or subcutaneous drug delivery;

FIG. 3 is a schematic drawing of another needle breaching the skin forintradermal or subcutaneous drug delivery;

FIG. 4 is a schematic drawing of another needle;

FIGS. 5( a) and 5(b) are schematic drawings of a portion of a needlewithout an extended tip portion and a needle with an extended tipportion, respectively;

FIG. 6 is schematic drawing of a mould halve 600 used for fabricating aneedle;

FIG. 7 is a schematic drawing of a portion of a mould halve used forfabricating a needle;

FIG. 8 is a schematic drawing of a mould halve of another mould halveused for fabricating another needle;

FIGS. 9( a)-9(c) are schematic drawings showing a top view of a processfor making a production mould halve for use in fabricating needles;

FIGS. 10( a)-10(c) are schematic drawings showing a top view of anotherprocess for making a production mould halve for use in fabricatingneedles;

FIGS. 11( a)-11(c) are schematic drawings showing a top view of aprocess for making an intermediate mould halve;

FIGS. 12( a)-12(c) are schematic drawings showing a top view of anotherprocess for making an intermediate mould;

FIGS. 13( a) and 13(b) are schematic drawings showing a top view of aprocess for making a production mould halve using an intermediate mouldhalve;

FIGS. 14( a) and 14(b) are schematic drawings illustrating anintradermal delivery mode and a subcutaneous delivery mode,respectively; and

FIGS. 15( a)-15(c) are schematic drawings of how skin is compressed andtensioned prior to application of the needle to the skin.

DETAILED DESCRIPTION

A schematic isometric view of a needle 100 and a schematic drawing ofthe needle 100 are shown in FIG. 1( a) and FIG. 1( b), respectively. Theneedle 100 comprises a base portion 102, a stem portion 104 extendingfrom the base portion 102, and a tip portion 106 formed on the stemportion 104. The base portion 102 comprises a connection adapter 102(e.g. a luer-lock connector) for coupling to a syringe (not shown) suchthat the needle 100 is interconnected to the syringe. Alternatively, thebase portion 102 can comprise a barrel portion adapted for coupling to aplunger.

The tip portion 106 comprises two dispensing ports 108. The twodispensing ports 108 are disposed opposite one another on sides of thetip portion 106 (hence termed side-ports). A lumen structure 118 extendswithin the needle 100 from the base portion 102 to the stem portion 104and to the tip portion 106. The lumen structure 118 leads to the twoside-ports 108 such that the lumen structure 118 is in fluid connectionwith the two side-ports 108. The lumen structure 118 terminates at thetwo side-ports 108 leaving a distance between the side ports 108 and anapex 114 of the needle 100. The lumen structure 118 comprises aplurality of lumen sections 118(a)-(c) with different widths/diameters,as shown in FIG. 1( b). The diameter of the lumen sections 118(a)-(c)are in descending size starting from the lumen section 118(a) of thebase portion 102 of the needle 100. The extent to which thewidth/diameter of the lumen structure 118 intersects with the tipportion 106 of the needle 100 determines the size of the side ports 108.

The base portion 102, the stem portion 104 and the tip portion 106 ofthe needle are formed integrally. Further, the base portion 102, thestem portion 104 and the tip portion 106 are formed from the samematerial and the entire needle 100 is made from plastic. Alternatively,the base portion 102, the stem portion 104 and the tip portion 106 ofthe needle 100 can be made using different materials. Methods offabricating the needle 100 will be described in greater detail withreference to FIGS. 6 to 13.

The needle 100 is approximately between 3 mm to 12.7 mm in length. 50microns to 1000 microns The lumen section 118(c) can have awidth/diameter ranging from about 50 microns to about 200 microns. Thelumen section 118(b) can have a width/diameter ranging from about 100microns to 1000 microns. The lumen section 118(a) can have awidth/diameter ranging from about 1 mm to 10 mm. The length of the stemportion 104 is chosen such that the needle 100 can be used forintradermal or subcutaneous drug delivery. It will be appreciated thatthe length of the stem portion and the lumen structure can have otherdimensions or geometries depending on the mode of drug delivery requiredand design requirements. At least one of the lumen sections118(a)-118(c) can be tapered, for example, the lumen section 118(c) canhave a width/diameter of about 50 microns at one end and awidth/diameter of about 200 microns at the other end. Similarly, thelumen sections 118(b) and 118(c) can also be tapered accordingly. Itwill be appreciated that the lumen structure 118 can be of variousshapes, for example, circular or rectangular, etc.

The base portion 102 and the stem portion 104 are cylindrical in shapeand the tip portion 106 is generally conical in shape. It will beappreciated that other geometries are possible, for example, the tipportion 106 can be pyramid shape, hexagonal shape, etc.

A schematic drawing of a needle 200 breaching the skin 220 forintradermal or subcutaneous drug delivery is shown in FIG. 2. After thestratum corneum 220 of the skin is breached by the needle 200, theneedle is inserted further within the skin such that the side ports 208of the needle reach a desirable depth. For intradermal delivery, theneedle is inserted within the dermis layer 224 below the epidermis layer222 of the skin, as shown in FIG. 2. For subcutaneous delivery (e.g.intramuscular delivery), the needle 200 is inserted beyond the dermislayer 224 and into the muscle layer 226. The drug to be dispensed passesthrough the lumen 218 and is delivered into the body via the side-ports208, as indicated by the arrows in FIG. 2.

A schematic drawing of a portion of another needle 300 breaching theskin for intradermal or subcutaneous drug delivery is shown in FIG. 3,each side port 308 of the needle 300 comprises an inwardly chamferedarea 322 at a lower portion of the side port 308 towards the stemportion 304 of the needle 300. The inwardly chamfered areas 322 help todispense drugs more effectively and minimises clogging of the side ports308 during penetration of the needle 300 into the skin. A portion of theside port 308 together with the apex 318 of the needle 300 serve thepurpose of breaching the skin 320 and subsequently expanding and holdingthe skin in place, so that the drugs can be dispensed through the sideports 308, first into the clearance created by the chamfered areas 322and then into the body. For intradermal delivery, the needle is insertedwithin the dermis layer 324 below the epidermis layer 326 of the skin,as shown in FIG. 3. For subcutaneous delivery (e.g. intramusculardelivery), the needle 200 is inserted beyond the dermis layer 324 andinto the muscle layer 328.

The distance between the side ports and the apex of the needle, termedthe submerged distance, is chosen such that when the needle is used tobreach the skin, the distance of the side ports from the apex of theneedle is sufficiently far enough for the side ports to be isolated fromthe breaching and compressing action of the skin yet close enough to theapex of the needle such that the side-ports can be completely buriedwithin the body for effective drug dispensing without spillage. Anotherconsideration is that the nearer the side-ports are to the apex, theweaker the mechanical structure of the needle is. Depending on thematerials used, the geometry of the needle and the size and number ofthe side-ports, the distance between the centre of the side-port fromthe apex of the needle can vary around 200 microns approximately, forexample, between about 100 to 500 microns, for a needle with a tipportion of about 1000 microns in length. The length of the entire needlecan range from about 1 mm to 10 mm in length.

In the needles described above, each needle comprises two side-ports. Itwill be appreciated that at least one side-port (in fluid communicationwith the lumen) is required to allow dispensation of the drugs and thenumber of side ports required can be varied depending on designrequirements.

FIG. 4 shows a schematic drawing of another needle 400. In addition totwo side-ports 408 and the lumen structure 418, the needle 400 comprisesan extended tip portion 424 formed on the tip portion 406. The extendedtip portion 424 forms the apex of the needle 400. The extended tipportion 424 comprises a substantially elongate protrusion extending fromthe tip portion 406 of the needle 400. It will be appreciated that ageometry of the extended tip portion 424 can be substantially the sameor different from a geometry of the tip portion 406. The extended tipportion 424 can be of other dimensions, for example, less than 50 μm ifrequired, depending on design requirements.

The needle 400 comprising the base portion 402, the stem portion 404,the tip portion 406 and the extended tip portion 424 are formedintegrally. Further, the base portion 402, the stem portion 404, the tipportion 406 and the extended tip portion 424 of the needle 400 areformed from the same material. Alternatively, the base portion 402, thestem portion 404 and the tip portion 406 of the needle 400 can be formedfrom different materials.

The needles described above can be made from polymers, for example,various grades of polycarbonate (PC), polystyrene (PS), and particularlybio-compatible polymers such as polyetherimide (PEI),polyetherehterketone (PEEK), etc. The type of polymer used to make theneedle is chosen based on characteristic mechanical properties of thepolymer that are suitable for specific dimensions of the needle designedfor specific applications. In addition, each polymer can be filled withadditives for the purposes of reinforcement and/or conductivity of theneedle.

FIGS. 5( a) and 5(b) are schematic drawings of a portion of a needle 502without an extended tip portion and a needle 504 with an extended tipportion 506, used to breach the stratum corneum (SC) of skin 508 forintradermal or subcutaneous drug delivery. The side ports of the needles502, 504 are not shown in FIGS. 5( a) and 5(b). The extended tip portion506 of the needle 504 in FIG. 5( b) has the same width as an apex 510 ofthe needle 502 without the extended tip portion. Due to the highlydeformable nature of skin (which is also viscoelastic), initial contactwith the apex 510 of the needle 502 normally deforms and tensions theskin 508 for a signification portion of an advancing stroke of theneedle 502 before breach of the skin 508 occurs. During this deformationstage, the skin 508 is forced to conform to the shape of the needle 502,particularly to the geometry of the apex 510. Therefore, comparing theneedle 502 without the extended tip and the needle 504 with the extendedtip portion 506, the needle 502 with a “normal” tip (i.e. without anyextended tip portion) causes full conformance of the skin 508 to thegeometry of the tip 510. This in turn results in a larger effectivecontact area between the skin 508 and the needle, as shown in FIG. 5(a). The effective contact areas are indicated by the bold lines in FIGS.5( a) and 5(b). Since a threshold pressure must be reached before anypuncturing or breach of the SC of the skin 408 can occur, a largercontact area reduces the resultant pressure caused by the apex 510 ofthe needle 502 on the skin 508 and makes breaching of the SC moredifficult as more force has to be applied. However, for the needle 504with the extended tip portion 506, the effective contact area betweenthe skin and the needle 504 is restricted to the apex 512 of theextended tip portion 506 which has a smaller area compared to theeffective contact area in FIG. 5( a). As a result of the reducedeffective contact area, a higher pressure is exerted on the skin by theneedle 504 and less force is applied to breach the SC of the skin 508.

A schematic drawing of a mould halve 600 used for fabricating a needleis shown in FIG. 6. Two identical mould halves 600 are used to form amould (not shown), therefore, only one mould halve 600 is shown anddescribed. The mould halve 600 in FIG. 6 can be used to fabricate, forexample, the needle 100 in FIGS. 1( a) and 1(b). The mould halve 600comprises a cavity 604 defining a periphery of a negative shape of theneedle to be fabricated, (e.g. needle 100 in FIG. 1( a)) The cavity 604comprises a base portion 610, a stem portion 612 extending from the baseportion 610, a tip portion 614 and two slots 608 for aligning an insert606 with reference to the cavity 604. Each of the portions 610, 612, 614defining a negative shape of the corresponding portions of the needle tobe fabricated. The insert 606 is in the form of an elongate pinstructure comprising a plurality of integral rectangular sections606(a)-(c) with different widths/diameters generally corresponding tothe size of the corresponding lumen sections of the needle to befabricated. The diameter of the sections 606(a)-(c) of the insert 606are in descending size starting from the base section 606(a).

During fabrication of the needle, the pin structure 606 is inserted intothe mould halves 600 and the pin structure 606 is aligned with thecavity 604 such that a leading edge 620 of the pin 606, in this case,leading corners 622 of the rectangular section 606(c) of the pin 606intersect with the periphery of the cavity 604 at two locations (i.e. attwo opposing walls defining the cavity) to form, the side ports (e.g.the side ports 108 of the needle 100 in FIG. 1( a)). The dashed linesrepresent the position of the pin in the mould cavity 604 when the pin606 is inserted into the mould halve 600. Accordingly, the two slots 608are shaped to align and hold the pin 606 in position within the mouldhalve 600. The shape of the slots 608 corresponds to the shape of theleading corners 612 of the pin 606 to align and hold the pin 606 withinthe mould halves 600.

The needles described above are fabricated as an integral piece and canbe formed by, for example, injection moulding. Other types of mouldingcan also be used, for example, cast moulding, or derivatives of castmoulding or injection moulding such as thermoforming, insert moulding,compression moulding, transfer moulding, multi-shot moulding, etc. Thederivatives can incorporate various add-on features to achieve specificprocess requirements. The add-on features may comprise external systemssuch as vacuum pump, robotic arms, etc. The various portions (i.e. thebase portion, the stem portion and the tip portion) of the needlesdescribed in above can be made from the same material. It will beappreciated that the various portions of the needles can be made fromdifferent materials. For example, the stem portion and the tip portionof the needle can be made from a material with particular mechanical andbio-compatibility properties while the base portion is made from adifferent material with different mechanical and chemical properties.Different materials can be used to fabricate the various portions of theneedle by multiple moulding of the various portions using variousmoulding processes known in the art.

A pair of mould halves 600 are aligned and held together tightly suchthat the cavity on one mould halve 600 faces the cavity on the othermould halve, before the pin 606 is inserted into the mould and alignedwith respect to the mould cavity 604. The periphery of the negativeshape of the needle is substantially parallel to an interface of themould halves 600 when the mould halves 600 are held together. The twomould halves 600 are closed and held tightly together before the pin 606is inserted into the mould and aligned with respect to the mould cavity604. The mould cavity 604 is then filled with a polymer melt, forexample, by using injection moulding, to form the needle. The polymermelt (not shown) is injected into the mould with an appropriate pressureto substantially fill the mould cavity 604. The molten polymer will flowaround the pin 606 such that portions of the mould cavity 604 occupiedby the pin 606 are not filled with the polymer melt, thereby creatingthe lumen (e.g. lumen 118 of the needle 100 of FIG. 1( a)), while theintersection of the leading edge 620 of the pin 606 with the peripheryof the mould cavity 604 creates the side ports of the needle (e.g. theside ports 108 of the needle 100 of FIG. 1( a)).

FIG. 7 is a schematic drawing of a portion of a mould halve 700 showingthe tip portion 716 of the mould cavity 704. The mould halve 700 can,for example, be in the form of the mould halve 600 of FIG. 6. Thesubmerge distance, a, of the needle (not shown in FIG. 7) is determinedby the distance from a tip 714 of the cavity 704 to the intersection ofthe leading edge 710 of the pin 706 with the periphery of the cavity704, while the extent to which the pin 706 intersects the periphery ofthe cavity 704 (i.e. distance b in FIG. 7) determines the size of theside ports in the needle to be fabricated.

It will be appreciated that the shape of the cavity in the mould halvedepends on the shape of the needle to be fabricated and can be ofvarious shapes other than triangular. If only one dispensing port isrequired in the needle, then the leading edge of the pin can be made toonly intersect with the periphery of the cavity at one location. Thenumber of side-ports created in the needle therefore depends on thenumber of locations where the leading edge of the pin intersects withthe periphery of the mould cavity. This can be achieved by differentcombinations of the shape of the mould cavity and the shape of the pin.For example, a conical mould cavity with a hexagonal pin will have sixports, while a hexagonal pyramid cavity with a circular pin will alsohave six dispensing ports. The pin can be of other shapes, for example,cylindrical, polygonal, etc., instead of rectangular, depending ondesign requirements. Accordingly, depending on the geometry of the pin,the slot can be round or polygonal, etc.

It will be appreciated that the mould or mould halve 600 of FIG. 6, forexample, be modified to comprise a plurality of cavities 604 arrangedside by side. Furthermore, a plurality of moulds can, for example, bestacked onto one another to fabricate a plurality of needles.

A schematic drawing of another mould halve 800 used for fabricating aneedle is shown in FIG. 8. The mould halve 800 in FIG. 8 can be used tofabricate, for example, the needle 400 in FIG. 4. It will be appreciatedthat a mould (not shown in FIG. 8) comprising two identical mould halves800 is used for fabricating the needle. Therefore, only one mould halve800 is shown and described.

The mould cavity 802 comprises two slots 804 for aligning and holding apin (not shown in FIG. 8), and vent 806 configured for creating theextended tip portion 424 of the needle 400 in FIG. 4. The vent 806 isformed on the tip portion 808 of the mould cavity 802. The vent 806 isgenerally an elongate channel extending at or near the tip portion 808of the mould cavity 802.

The dashed lines in FIG. 8 show the position of the insert (not shown)when the insert is placed within the mould cavity 802.

The needle can be moulded by, for example, using injection moulding tofill the mould cavity 802 with polymer melt. A polymer melt (not shown)is injected into the mould with an appropriate pressure to substantiallyfill the mould cavity 802 in the mould.

Polymer melt is generally viscous and therefore has difficulty fillingmould cavities. This becomes a significant problem when moulding objectsof small dimensions, for example, at the tip portion of the needle wherethe dimensions can be about 10-100 microns in size. Air in the mouldcavities is pushed by the polymer melt during moulding and trapped inthe mould cavity forming voids in the moulded object. For example, aircan be trapped near or at the tips of the mould cavities, causing thetip portion and the apex of in the resulting needle to be less sharp andnot well defined.

By using a mould with a vent, for example, the vent 806 in FIG. 8, asthe polymer melt fills the mould cavity 802, air trapped in the mouldcavity 802 is vented out of the mould via the vent 806. When the mouldcavity 802 is substantially filled with the polymer melt, additionalpressure is applied to the polymer melt such that the polymer meltpartially fills the vent 806 to form the extended tip portion of theneedle to be fabricated, e.g. the extended tip portion 424 of the needle400 in FIG. 4. Therefore, the vent 806 is configured for creating theextended tip portion 424 of the needle 400 in addition to provide forventing of air out of the mould cavity 802. The length of the extendedtip portion 424 of the needle 400 is accordingly determined by the levelof polymer melt filling the vent 806. Injection moulding can be carriedout in a vacuum chamber to remove any residual air trapped in the mouldcavities and to assist the polymer melt in entering and filling theneedle cavities. Further, a vacuum oven can be used to melt the polymer.

It will be appreciated that the mould halve 600 shown in FIG. 6 can alsocomprise a vent formed on the tip portion 614 of the mould cavity 604 asdescribed above for venting of air out of the mould cavity 604. In orderto create needles without the extended tip, for example, the needle 100in FIGS. 1( a) and 1(b), an appropriate pressure is applied to thepolymer melt during the injection molding process such that the polymermelt does not fill the vent.

It will be appreciated that the pin can have different geometries andsections with different widths/diameters, depending on designrequirements. The shape of lumen created will depend on the geometry ofthe pin. In general, the lumen defines a periphery of a negative shapeof the pin. The pin may comprise different geometry and/or dimension ata stem portion and at the leading edge, for example, when a larger lumenis required to reduce dispensing pressure of the drug and a particularsize of side-ports are required. Alternatively, the pin can be madetapered.

As described above, the mould halves (e.g. the mould halve 800 in FIG. 8or the mould halve 600 FIG. 6) used to fabricate the needles comprisescavities that generally define a periphery of a negative shape of theneedles to be fabricated. One way of creating the mould halve is tofirst create a master mould comprising a positive shape of the needles.In other words, the master mould comprises protrusions that aregenerally corresponding to the shape of the needles that are to befabricated. The protrusions on the master mould can be fabricated byprecision wire-cutting or other precision engineering means. The patternof the protrusions corresponding to the shape of the needles on themaster mould is then transferred onto a production mould or anintermediate mould by, for example, hot embossing, to form cavitiescorresponding to a negative shape of the needles.

Schematic drawings showing a top view of a process for making aproduction mould halve 900 (FIG. 9( c)) for use in fabricating needlesare shown in FIGS. 9( a)-9(c). The production mould halve 900, can be inthe form of, for example, the mould halve 800 in FIG. 8, and can be usedto form, for example, the needle 400 of FIG. 4. The master mould 902comprises a plurality of protrusions 904 corresponding to the shape ofthe needles (e.g. needle 400 of FIG. 4) to be fabricated is firstcreated. The master mould 902 is made of tool steel. The protrusions 904on the master mould 902 can be made by precision wire cutting.Generally, the shape of the protrusions 904 on the master mould 902 arepositive images of the needles to be fabricated. The protrusions 904comprise extended tip portions 906. The extended tip portions 906 of theprotrusions 904 are used to form vents 914 in the production mould halve900. Each protrusion 904 comprises two triangular shaped shoulderportions 908 protruding from two opposing sidewalls 914. The twotriangular shaped shoulder portions 908 are used to form the slots 910in the cavity 912 of the production mould halve 900. It will beappreciated that the shoulder portions 916 can be of other geometriesdepending on the shape of the slot 910 that is required. Generally, ashape of the shoulder portions 916 is a positive shape of the slots 910in the production mould halve 900. In this case, since the pin (notshown) is rectangular in shape, the shape of the slots 910 aretriangular in shape and therefore, the shoulder portions 916 are alsotriangular in shape.

The master mould 902 mounted to a first heated platen 918 is hotembossed into a metal substrate 920 mounted on a second heated platen(not shown) to form a negative image of the master mould 902 (andtherefore a negative image of the needles) in the substrate 920. Themetal substrate 920 is placed below the master mould 902 and the mastermould 902 is lowered onto the metal substrate 920 to transfer the shapeof the needles on the master mould 902 onto the metal substrate 920 toform the cavities 912 comprising a periphery of a negative shape of theneedles on the metal substrate 920. The master mould 902 is then liftedfrom the metal substrate 920 after embossing (FIG. 9( c)). The embossedsubstrate 920 forms the production mould halve 900 that is used forfabricating the needles. Two identical mould halves 900 are closedtogether tightly to form a mould (not shown). An edge portion 924 of theproduction mould halve 900 is removed, for example, by grinding, suchthat the vents 914 extend through the production mould halve 900. Itwill be appreciated that alternatively, the extended tip portions 906 ofthe master mould 900 can be made longer such that the vents 914 extendthrough the edge portion 924 of the substrate 920 during hot embossing(i.e. no grinding of the edge portion 924 is required).

Schematic drawings showing a top view of another process for making aproduction mould halve 1000 for use in fabricating needles are shown inFIGS. 10( a)-10(c). The production mould halve 1000, can be in the formof, for example, the mould halve 800 in FIG. 8, and can be used to form,for example, the needle 400 of FIG. 4. In this example, microforming isused to fabricate the needles. The master mould 1002 comprising theprotrusions 1004 is mounted to a punch 1006. A metal sheet 1008 isplaced on a deformable die (not shown) such that the metal sheet 1008 isbetween the punch 1006 and the deformable die. The metal sheet 1008 canbe made of metallic materials such as steel, aluminium and copper. Thethickness of the metal sheet 1008 can range from about 0.05 mm to about0.5 mm. However, other dimensions, for example, a thickness of greaterthan 0.5 mm can also be used depending on design requirements. The punch1006 together with the master mould 1002 is moved towards the metalsheet 1008 and presses against the metal sheet 1008 and the deformabledie. The metal sheet 1008 is deformed and a negative shape of theprotrusions 1004 of the master mould 1002 is formed onto the metal sheet1008. Therefore, the metal sheet 1008 comprises cavities 1012 generallydefining the periphery of the negative shape of the needles to beformed. At the same time, the deformable die is also deformed by theprotrusions 1004 of the master mould 1002 to form cavities defining thenegative shape of the protrusions 1004. The punch 1004 together with themaster mould 1002 is then retracted (FIG. 10( c)). The deformed metalsheet 1008 in FIG. 10( b) is removed and a thickness reinforcementprocess, for example, metal deposition is performed on an underside (notshown) of the metal sheet 1008 defining an exterior surface of thecavities 1012 to form the production mould halve 1000 used forfabricating the needles. Other methods of fabricating the productionmould halve are also possible, for example, by first fabricating anintermediate mould halve using the master mould and subsequentlyfabricating the production mould halve using the intermediate mouldhalve.

Schematic drawings showing a top view of a process for making anintermediate mould halve 1100 are shown in FIGS. 11( a)-11(c). Asdescribed earlier, the master mould 1102 comprises protrusions 1104 thatare generally corresponding to the shape of the needles that are to befabricated. The protrusions 1104 on the master mould 1104 are made oftool steel and can be fabricated by precision wire-cutting or otherprecision engineering means. The master mould 1102 mounted to a firstheated platen 1106 is hot embossed into a polymer substrate 1108 mountedon a second heated platen (not shown) to form a negative image of theprotrusions 1104 of the master mould 1102 (and therefore a negativeimage of the needles) in the polymer substrate 1108. The resultingembossed polymer substrate 1100 (i.e. the intermediate mould) comprisingcavities 1112 defining a negative image of the protrusions (andtherefore, a negative image of the needles) is then used to fabricatethe production mould halve (not shown in FIGS. 11( a) to 11(c)) forfabricating needles.

Schematic drawings showing a top view of another process for making anintermediate mould halve 1200 are shown in FIGS. 12( a)-12(c). In thisexample process, the intermediate mould halve 1200 is cast moulded. Themaster mould 1202 comprising the protrusions 1206 forms part of acasting mould 1208 used in the casting process. Molten polymer 1210 intothe casting mould 1208 and over the master mould 1202 as shown in FIG.12( b). The molten polymer 1210 is allowed to cure and removed from thecasting mould 1208 to obtain the intermediate mould halve 1200comprising cavities 1212 defining a negative shape of the needles to befabricated. Each protrusion 1206 includes an extended tip portion 1216for forming an air vent 1218 in the intermediate secondary polymericmould 1200.

The polymeric intermediate mould halves described in FIGS. 11( a)-11(c)and FIGS. 12( a)-12(c) may be made of various types of polymers such aspolycarbonate (PC), polystyrene (PS), polyetherimide (PEI),polypropylene (PP), polyethylene (PE), etc. in sheet form orpoly(dimethylsiloxane) (PDMS) in liquid form for cast moulding.

Schematic drawings showing a top view of a process for making aproduction mould halve 1300 using an intermediate mould halve 1302 areshown in FIGS. 13( a) and 13(b). The intermediate mould halve 1302 can,for example, be in the form of the intermediate mould halve 1200 inFIGS. 12( a)-12(c) or the intermediate mould halve 1100 in FIGS. 11(a)-11(c). As described above, the intermediate mould halve 1302comprises cavities 1304 defining a negative shape of the needles to befabricated. A layer of metal 1306 (represented by the shaded regions inFIG. 13( b)) is deposited onto the intermediate mould halve 1302 andinto the cavities 1304 of the intermediate mould halve 1302 (e.g. bychemical or vapour deposition, electroforming, electroplating, etc.).The deposited layer of metal 1306 comprising cavities 1308 is removedfrom the intermediate mould halve 1302 as shown in FIG. 15( b). Thedeposited layer of metal 1306 is subjected to a thickness reinforcementprocess, for example, metal deposition performed on an underside (notshown) of the deposited metal layer 1306 defining an exterior surface ofthe cavities 1308 to form the production mould halve 1300 used forfabricating the needles.

In the embodiments described above, the polymer used for making theintermediate mould halve is chosen to have a certain elasticity anddeformability characteristic such that the intermediate mould halves canbe re-used. A mould release agent can be applied or sprayed onto theintermediate mould before metal deposition is performed on theintermediate mould. This allows effective release of the deposited metallayer and at the same time preserves the intermediate mould halve fromdamage to allow subsequent use.

Since the needles described above and the base portion in the form ofe.g. a luer-lock connector are formed as an integral piece, separateassembling of the needle and the luer-lock connector is eliminated.Machining costs are also eliminated, as post fabrication machining isnot required. On the other hand, conventional steel needles are requiredto be separately assembled to a luer-lock connector and may require postfabrication machining. Further, ploymeric needles have the freedom totake any other form which may be impossible or not cost effective forthe fabrication of stainless steel needles.

FIGS. 14( a) and 14(b) are schematic drawings illustrating intradermal,and subcutaneous drug delivery modes, respectively.

The intradermal delivery mode (see FIG. 14( a)) involves insertion ofneedle 1400 past the stratum corneum (SC) 1402 and into the epidermis1406 and/or the dermis 1408 layer of the skin (i.e. within the thicknessof the skin). Typically the SC 1402 is approximately 10-20 μm, theepidermis 1406 is approximately 0.1-0.2 mm (i.e. 100-200 μm) and thedermis 1414 is approximately 1.0-2.0 mm. The length of the stem portion1414 of the needle 1400 is chosen such that the needle can be used forintradermal and subcutaneous drug delivery, for example, by injecting aliquid into the body. As described above, the base portion 1416 of theneedle 1400 comprises a connection adapter (e.g. a luer-lock connector)for coupling to a dispensing apparatus such as a syringe 1418 such thelumen structure 1420 is in fluid communication with a reservoir 1422within the syringe 1418. During drug delivery, drugs stored in thereservoir 1422 are dispensed into the dermis layer 1408 of the skin viathe side ports 1424.

The needle 1400 can also be used for extracting body fluid, which mayinclude whole blood sampling. Body fluid can be extracted from the bodye.g. from blood capillaries, via the side ports 1424 and the lumenstructure 1420 for whole blood sampling. The extracted body fluid can bestored in the reservoir 1422 in the syringe 1418.

Alternatively, the base portion 1416 can comprise a barrel portionadapted for coupling to a plunger 1426.

The base portion 1416 of the needle 1400 can be made from a differentmaterial from the stem portion 1414 and the tip portion 1424 of theneedle 1400. Since the base portion 1416 is used for coupling to adispensing apparatus, a material with suitable mechanical properties isused to make the base portion 1416. On the other hand, since the tipportion 1242 and the stem portion 1414 are to be inserted into the body,the tip portion 1242 and the stem portion 1414 can be made from amaterial with bio-compatible properties. It will be appreciated that theentire needle 1400 can also be made from a single material.

The subcutaneous delivery mode (see FIG. 14( b)) involves insertion of aneedle 1400 beyond the thickness of the skin where the drug can beinjected, for example, in between the skin and muscles 1412. Furtherdrug delivery modes, for example, intravenous delivery (not shown)involving insertion of the needle into a vein for direct injection ofdrug into blood streams and intramuscular delivery (not shown) involvinginsertion of the needle into muscles are generally classified as a typeof subcutaneous delivery mode as both the intravenous and intramusculardelivery modes involve insertion of the needle beyond the thickness ofthe skin.

The penetration depth of the needle is linearly related to the length ofthe needle (in particular the stem portion of the needle) when it isfully plunged into the skin. Although a significant portion of theneedle's length goes into the skin after penetration, a portion of theneedle, for example the base portion and a portion of the stem portionof the needle stays outside of but in contact with the skin due to skindeformation. For this reason, the length of the stem portion requiredshould generally be greater than a targeted penetration depth. Theextended tip portion of the needles (e.g. the needle 400 in FIG. 4) canreduce the discrepancy between the length of the needle and the targetedpenetration depth as less deformation of the skin occurs, therebyachieving more accurate penetration depth.

One way to achieve variable penetration depth using a needle is torestrict the penetrating length of the stem portion of the needle by anexternal means, for example a mechanical limiter with a turn-able capand screw thread, or any other similar mechanical means that providessimilar functions, to adjust the penetrating length of the stem portionof the needle. Alternatively a double-sided adhesive tape with a desiredthickness that provides a clearance distance can be disposed near or atthe base portion of the needles to limit the depth of penetration of thestem portion of the needle. The adhesive tape may have an elasticcharacteristic such that the adhesive tape springs back to its originalthickness after the initial compression during penetration. The adhesivetape also provides fixation of the needle module onto the skin afterbreaching of the SC. Another way is to stop the advancing stroke of theneedle once the desired depth is reached.

The penetration depth of the needle can also be limited by covering thebase portion or the stem portion near the base portion of the needlewith a solid layer (rigid epoxy or compressible adhesive tape) therebyreducing the effective length of the stem portion of the needle.

Skin tensioning and compression may be required prior to the breachingof the SC for intradermal or subcutaneous drug delivery to increasepenetration effectiveness. This can be achieved, for example, by using amiddle 1500 finger and a thumb 1502 to compress the skin (FIG. 15( b))and tension the skin 1504 (FIG. 15( c)), and pressing the skin with theneedle platform using appropriate force, as shown in FIGS. 15( a) to15(c).

It will be appreciated by a person skilled in the art that numerousvariations and/or modifications may be made to the present invention asshown in the specific embodiments without departing from the spirit orscope of the invention as broadly described. The present embodimentsare, therefore, to be considered in all respects to be illustrative andnot restrictive.

1. A needle comprising: a base portion; a stem portion extending fromthe base portion; a tip portion formed on the stem portion, the tipportion having a solid apex; a lumen extending within the needle, thelumen extending from the base portion to the stem portion and the tipportion; wherein a length of the stem portion is chosen such that theneedle can be used for intradermal or subcutaneous drug delivery or bodyfluid extraction, and the base portion, the stem portion and the tipportion are integrally formed.
 2. A needle as claimed in claim 1,wherein the base portion, the stem portion and the tip portion areintegrally formed from the same material.
 3. The needle as claimed inclaim 1, wherein at least one of the base portion, the stem portion orthe tip portion is integrally formed from a different material.
 4. Theneedle as claimed in claim 1, further comprising: at least one sideport, wherein the side port extends into the lumen such that the sideport and the lumen are in fluid communication with each other.
 5. Theneedle as claimed in claim 4, wherein the lumen comprises a plurality ofsections, each section having a different diameter or width.
 6. Theneedle as claimed in claim 5, wherein the diameter or widths of theplurality of sections is in descending order starting from a basesection of the lumen.
 7. The needle as claimed in claim 4, wherein thelumen is tapered.
 8. The needle as claimed in claim 3, comprising: twoor more side ports disposed on the tip portion of the needle.
 9. Theneedle as claimed in claim 1, further comprising an extended tip portionformed on the tip portion, the extended tip portion forming an apex ofthe needle, wherein the extended tip portion comprises a substantiallyelongate protrusion extending from the tip portion.
 10. The needle asclaimed in claim 9, wherein a geometry of the extended tip portion issubstantially the same as a geometry of the tip portion.
 11. The needleas claimed in claim 1, wherein the base portion comprises a connectionadapter for coupling to a dispensing apparatus.
 12. The needle asclaimed in claim 1, wherein the base portion comprises a luer lockstructure for interconnecting the needle to a syringe.
 13. The needle asclaimed in claim 1, wherein the base portion comprises a barrel portion,the barrel portion being adapted for coupling to a plunger.
 14. Theneedle as claimed in claim 1, wherein the needle is made from at leastone of a group of polymers consisting of polycarbonate (PC), polystyrene(PS), polyetherimide (PEI), or polyetherehterketone (PEEK).
 15. Theneedle as claimed in claim 1, wherein the needle is fabricated usinginjection moulding or cast moulding or derivatives of cast moulding orinjection moulding.
 16. A method of fabricating a needle, the methodcomprising: forming a base portion; forming a stem portion extendingfrom the base portion; forming a tip portion formed on the stem portion,the tip portion having a solid apex; forming a lumen extending withinthe needle, the lumen extending from the base portion to the stemportion and the tip portion; wherein a length of the stem portion ischosen such that the needle can be used for intradermal or subcutaneousdrug delivery or body fluid extraction, and the base portion, the stemportion and the tip portion are integrally formed.
 17. The method asclaimed in claim 16, wherein the base portion, the stem portion and thetip portion are integrally formed from the same material.
 18. The methodas claimed in claim 16, wherein at least one of the base portion, thestem portion or the tip portion is integrally formed from a differentmaterial.
 19. The method as claimed in claim 16, further comprising:forming at least one side port, wherein the side port extends into thelumen such that the side port and the lumen are in fluid communicationwith each other.
 20. The method as claimed in claim 16, wherein thelumen comprises a plurality of sections, each section having a differentdiameter or width.
 21. The method as claimed in claim 20, wherein thediameter or widths of the plurality of sections is in descending orderstarting from a base section of the lumen.
 22. The method as claimed inclaim 19, wherein the lumen is tapered.
 23. The method as claimed inclaim 19, the method further comprising: two or more side ports disposedon the tip portion of the needle.
 24. The method as claimed in claim 16,further comprising: forming an extended tip portion on the tip portion,wherein the extended tip portion forms an apex of the needle and theextended tip portion comprises a substantially elongate protrusionextending from the tip portion.
 25. The method as claimed in claim 16,wherein the base portion comprises a connection adapter for coupling toa dispensing apparatus.
 26. The method as claimed in claim 16, whereinthe base portion comprises a luer lock structure for interconnecting theneedle to a syringe.
 27. The method as claimed in claim 16, wherein thebase portion comprises a barrel portion, the barrel portion beingadapted for coupling to a plunger.
 28. The method as claimed in claim16, further comprising: forming a master mould comprising a positiveshape of the needle; using the master mould to form a production mouldcomprising a cavity comprising a periphery of a negative shape of theneedle; and using the production mould to form the needle.
 29. Themethod as claimed in claim 28, comprising: forming the master mouldcomprising a positive shape of the needle; using the master mould toform an intermediate mould comprising a cavity comprising a periphery ofa negative shape of the needle; and using the intermediate mould to formthe production mould.
 30. The method as claimed in claim 28, comprising:forming a pair of production mould halves, each production mould halfcomprising a cavity comprising a periphery of a negative shape of theneedle; using the pair of production mould halves to form the needle.31. The method as claimed in claim 29, comprising: forming a pair ofintermediate mould halves, each intermediate mould half comprising acavity comprising a periphery of a negative shape of the needle; usingthe pair of intermediate mould halves to form a pair of production mouldhalves.
 32. The method as claimed in claim 30, wherein the pair ofproduction mould halves are identical to each other, each productionmould half comprising a plurality of cavities, each cavity comprising aperiphery of a negative shape of the needle.
 33. The method as claimedin claim 30, wherein the periphery of the negative shape of the needleis substantially parallel to an interface of the two production mouldhalves.
 34. The method as claimed in claim 30, wherein the intermediatemould halves are made from polymer.
 35. The method as claimed in claim30, further comprising: filling the cavity of the production mouldhalves with a polymer to form the needle.
 36. The method as claimed inclaim 28, wherein the positive shape of the needle on the master mouldis created by precision wire-cutting.
 37. The method as claimed in claim30, wherein the production mould halves are made of metal.
 38. Themethod as claimed in claim 30, the method further comprising: providingan insert member; providing the pair of production mould halves, each ofthe production mould halves further comprising at least one slot portionfor receiving and aligning the insert member such that a leading edge ofthe insert intersects the periphery of the negative shape of the needle;aligning the pair of production mould halves; inserting the insertmember into the production mould halves; and filling the productionmould halves with a fill material, wherein the insert creates the lumenin the needle and the intersection of the leading edge of the insertwith the periphery of the negative shape of the needle creates the sideport extending into the lumen such that the lumen and the side port arein fluid communication with each other.
 39. The method as claimed inclaim 30, wherein the periphery of the negative shape of the needlecomprises a channel extending from an apex of the negative shape of theneedle for forming the extended tip portion of the needle.
 40. Themethod as claimed in claim 39, further comprising filling the channel atleast partially to form the extended tip portion.
 41. The method asclaimed in claim 38, wherein the insert member comprises a pin having aplurality of sections, each section having a different diameter orwidth.
 42. The method as claimed in claim 41, wherein the pin istapered.
 43. A method of using a needle as claimed in claim 1 forinjecting liquid into a body.
 44. A method of using a needle as claimedin claim 1 for extracting body fluid from a body.
 45. The method ofusing the needle as claimed in claim 44, wherein extracting body fluidfrom the body includes whole blood sampling.
 46. The needle as claimedin claim 9, wherein a geometry of the extended tip portion is differentfrom a geometry of the tip portion.